Spatio-temporal patterns of early cortical folding may provide a clinically useful marker for identifying the early signs of neurodevelopmental disorders before variable and complex folding patterns appear. In vivo MRI and 2D slice-based visual inspection have been performed to assess brain cortical folding for fetal diagnosis. However, visual diagnosis may miss early folding abnormalities and quantitative and comprehensive information of the early cortical folding patterns from fetal MRI is incomplete. In addition, clinial relevance of MRI quantification of the early cortical folding has not been evaluated. The proposed project will quantify and define spatio-temporal dynamics of regional and global early cortical folding patterns in normal fetal brains, and develop a novel approach to analyze individual clinical fetal MRIs performed for neurological concerns. We will focus on early fetal brain development between 18 weeks gestational age (GA) (the earliest for routine clinical fetal MRI at Boston Children's Hospital) and 28 weeks GA using high-quality and high-resolution 3T fetal MRI. First, early cortical folds of primary sulci will be identified and anatomically labeledon the 3D cortical plate surface using advanced image post-processing techniques. We will investigate multivariate geometric and topological features (area, curvature, depth, 3D relative position and the number of folds) for each primary sulcus. Furthermore, our approach will consider not only the regional features of sulcal folds themselves but also inter-sulcal relationships to highlight the global patterning of cortical folding, which might be associated wit optimal cortical areal patterning and connections. Normal individual variability of the regional sulcal features will be determined at each GA for each primary sulcus, and their temporal dynamics will be modeled with a mathematical function. The spatio-temporal changes of global sulcal patterns will be examined using advanced spectral-based sulcal pattern matching and comparison technique. All imaging products and measurements from the normal fetal brains will be presented and freely accessible. Based on the normal dataset, we will identify and label the cerebral primary sulci, estimate GA and determine the similarity of early cortical folding patterns to the normal folding patterns in individual fetuses. The detailed information of quantitative feta MRI analysis will be correlated with a qualitative assessment of cerebral anatomy from follow- up neonatal MRI determined as a gold standard. We hypothesize that our MRI quantification will show high sensitivity and specificity, and show higher sensitivity in detecting abnormal gyrification at fetal stage compared to a qualitative fetal imaging assessment. It might provide the potential of our technology as a diagnosis assist to catch early signs of abnormal cortical growth that may be visually missed. We believe that this study will be the first step toward a practical clinical use of quantitative fetal MRI analysis for individual fetal diagnosis and will provide preliminary data for a more comprehensive prospective study and a larger clinical trial.